NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients

Leuk Res. 2014 May;38(5):619-24. doi: 10.1016/j.leukres.2014.03.001. Epub 2014 Mar 11.

Abstract

JAK2/STAT signaling promotes survival and expansion of myelodysplastic syndrome (MDS) clones, but little is known about the potential of JAK2/STAT as a therapeutic target in MDS. We investigated the effect of NS-018, a novel antagonist for JAK2, on the colony-forming ability of bone marrow mononuclear cells (BMMNCs) from high-risk MDS patients. NS-018 decreased colony-forming unit-granulocyte/macrophage (CFU-GM) colony numbers from MDS-derived BMMNCs in a dose-dependent manner, and this effect was significantly more potent than against normal BMMNCs. In addition, NS-018 suppressed the phosphorylation of STAT3 in colony-forming cells from MDS patients. Collectively, NS-018 could be a new therapeutic option for high-risk MDS.

Keywords: CFU-GM; JAK2; Myelodysplastic syndrome; NS-018; STAT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Marrow Cells / physiology*
  • Female
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Risk
  • STAT3 Transcription Factor / metabolism
  • Stem Cells / drug effects*

Substances

  • Protein Kinase Inhibitors
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Janus Kinase 2